MK2206 in Combination With Anastrozole, Fulvestrant, or Anastrozole and Fulvestrant in Treating Postmenopausal Women With Metastatic Breast Cancer

Inclusion Criteria

• •Patients must have histologically or cytologically confirmed invasive breast cancer that is metastatic stage IV or recurrent metastatic (histologic/cytologic confirmation of recurrence preferred, but not required)
• •Either the primary or the metastatic tumor must be positive for estrogen-receptor (\> 1% tumor cell staining by immunohistochemistry or an Allred score of \>= 3 by immunohistochemistry)
• •Patient must have measurable or non-measurable lesions (defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria)
• •* Note: to be eligible for the FDG PET imaging studies in Phase IA, the presence of measurable lesions of at least 1.5 cm or the presence of bone lesions is required
• •Patients may have undergone any number of prior lines of chemotherapy or endocrine regimens but must not have a history of disease progression on anastrozole (Phase IA and Phase IB), fulvestrant (Arm C), or both anastrozole and fulvestrant (Arm D)
• •* Phase IA and IB:
• •* Currently being treated with anastrozole with no evidence of disease progression OR
• •* Currently being treated with letrozole or exemestane with no evidence of disease progression and willing to switch to anastrozole for study enrollment OR
• •* Considering switching to anastrozole due to disease progression from the most recent anti-cancer therapy
• •* Arm C:
• •* Currently being treated with fulvestrant with no evidence of disease progression OR
• •* Considering switching to fulvestrant due to disease progression from the most recent anti-cancer therapy
• •* Arm D:
• •* Currently being treated with either anastrozole or fulvestrant with no evidence of disease progression OR
• •* Currently being treated with letrozole or exemestane with no evidence of disease progression and willing to switch to anastrozole for study enrollment
• •* Considering switching to anastrozole or fulvestrant due to disease progression from the most recent anti-cancer therapy
• •Patients must be postmenopausal women as defined by one of the following:
• •* Women \> 60 years
• •* Women =\< 60 years with spontaneous cessation of menses \> 12 months prior to registration
• •* Women =\< 60 years with cessation of menses of duration \< 12 months or secondary to hysterectomy AND an follicle stimulating hormone (FSH) level in the postmenopausal range according to institutional standards (or \> 34.4 IU/L if institutional range is not available) prior to registration
• •* Women =\< 60 years on hormonal replacement therapy who have discontinued hormonal therapy AND an FSH level in the postmenopausal range according to institutional standards (or \> 34.4 IU/L if institutional range is not available) prior to registration
• •* Status post bilateral surgical oophorectomy
• •* Premenopausal women on a gonadotropin-releasing hormone (GnRH) analog
• •Patients must have a life expectancy greater than 4 months
• •Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• •Leukocytes \>= 3,000/mcL
• •Absolute neutrophil count (ANC) \>= 1,500/mcL
• •Platelet count \>= 100,000/mcL
• •Total bilirubin not above the institutional upper limit of normal
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• •Creatinine not above the institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• •If patients have diabetes mellitus, fasting glucose must be =\< 120 mg/dL and hemoglobin (Hb)A1c =\< 8%
• •Women of childbearing potential must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, the patient should inform the treating physician immediately
• •Patients who are eligible for this study may also be eligible for and participate in National Cancer Institute (NCI) Protocol 9167, titled "Positron Emission Tomography (PET) with 18F-Fluoroestradiol (FES) as a Predictor of Response in Patients with Breast Cancer Scheduled to Be Treated with MK-2206 in Combination with Either an Aromatase Inhibitor or Fulvestrant on NCI Protocol 8762," in which case the FES-PET in Protocol 9167 has to be performed a minimum of 48 hours and a maximum of 30 days before the first dose of MK-2206; in addition, all FES-related side effects must have resolved before the first dose of MK-2206
• •Patients must have the ability to understand and the willingness to sign a written informed consent document